VIRUCIDAL EFFECT OF STIMULATED EOSINOPHILS ON HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1

Eosinophils, when stimulated, release a variety of agents that can be toxic to ingested or extracellular targets, Among these systems is one that consists of eosinophil peroxidase (EPO), H2O2, and a halide, We report here that phorbol myristate acetate (PMA)-stimulated human eosi nophils are virucidal to HIV-1 in a chloride-containing medium, When t he eosinophil concentration is decreased to a level at which the viruc idal effect is incomplete, the addition of bromide or iodide restored complete virucidal activity, The virucidal effect of eosinophils, PMA, and bromide under these conditions is inhibited by the peroxidase inh ibitor azide and catalase, but not heated catalase or superoxide dismu tase, implicating the EPO-H2O2-halide system, Purified EPO when combin ed with H2O2 in a chloride-containing medium is virucidal to HIV-1, Wh en the EPO concentration is suboptimal, virucidal activity is increase d by bromide, iodide, and, in this instance, thiocyanate and the viruc idal activity of the bromide-supplemented system is inhibited by azide and catalase, Our findings, together with the demonstration that eosi nophils express CD4 on their surface and, under some circumstances, ca n be productively infected with HIV-1, raise the possibility that biol ogical oxidants formed by eosinophils can influence the pathogenesis o f HIV-1 infection by their toxicity to eosinophil-associated or extrac ellular virus.